This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of the study is to provide an adjustable dosage, efficient means of analgesic drug delivery that has low abuse potential, wide therapeutic index, and results in dose-dependent drug absorption. Currently available analgesic patches are subject to patient abuse, have resulted in fatalities, been the subject of abuse, and are only available in fixed dosages. The goal is to develop a gel that can be applied to a patch to provide dose dependent absorption of analgesics. The study is currently evaluating the use of fentanyl in combination with naloxone. Naloxone is an opioid antagonist that antagonizes the euphoric, analgesic, and respiratory depressant effects of fentanyl. In vitro data demonstrated transdermal flux of fentanyl, but not naloxone, suggesting analgesia will be achieved with the gel formulation due to transdermal flux of fentanyl, but not naloxone. However if the gel were intentionally or unintentionally misused, such as eating or injecting the ingredients IV, the addition of naloxone will antagonize and prevent the euphoric and respiratory depressant effects of fentanyl resulting in a greater safety profile and lowering of the abuse potential. In vitro results suggested O-desmethyltramadol is not lipophilic enough to achieve transdermal flux, therefore the project has been focused on the addition of naloxone to the gel to minimize abuse and increase safety. The gel formulation for the patch containing fentanyl has been optimized using in vitro methods and is currently being assessed in vivo.